Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.
Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.
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DOI：
10.1038/s41467-021-27079-w
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发表时间：
2021-11-26
影响因子：
16.6
通讯作者：
Olopade OI
中科院分区：
文献类型：
--
作者：
Ansari-Pour N;Zheng Y;Yoshimatsu TF;Sanni A;Ajani M;Reynier JB;Tapinos A;Pitt JJ;Dentro S;Woodard A;Rajagopal PS;Fitzgerald D;Gruber AJ;Odetunde A;Popoola A;Falusi AG;Babalola CP;Ogundiran T;Ibrahim N;Barretina J;Van Loo P;Chen M;White KP;Ojengbede O;Obafunwa J;Huo D;Wedge DC;Olopade OI
与欧洲血统的白人女性相比，散居在外的非洲黑人女性患侵袭性乳腺癌的几率更高，死亡率更高。虽然种族间的种系变异是已知的，但尚未详细研究体细胞进化的差异。对来自尼日利亚妇女的97例乳腺癌的深层全基因组进行分析，其中一个子集进行RNA-seq分析，与癌症基因组图谱（n = 76）进行比较，揭示了更高的基因组不稳定性和增加的肿瘤内异质性，以及由早期克隆GATA3突变定义的独特基因组亚型，诊断时年龄年轻10.5岁。我们还发现了真正驱动因子（ZNF217和SYPL1）中的非编码突变，以及先前未报道的与非洲血统比例密切相关的INDEL特征，强调了在生物医学研究中扩大多样化人群的必要性。最后，我们证明了同源重组缺陷的肿瘤特征在患者分层中具有重要的临床意义。乳腺癌的异质性和肿瘤进化轨迹在非洲血统的妇女中仍然很大程度上是未知的。在这里，作者执行尼日利亚乳腺癌患者的全基因组和转录组测序，并确定独特的进化现象。
Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies. Breast cancer heterogeneity and tumour evolutionary trajectories remain largely unknown among women of African ancestry. Here, the authors perform whole genome and transcriptome sequencing of Nigerian breast cancer patients and identify unique evolutionary phenomena.
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影响因子：
82.9
作者：
Bernard E;Nannya Y;Hasserjian RP;Devlin SM;Tuechler H;Medina-Martinez JS;Yoshizato T;Shiozawa Y;Saiki R;Malcovati L;Levine MF;Arango JE;Zhou Y;Solé F;Cargo CA;Haase D;Creignou M;Germing U;Zhang Y;Gundem G;Sarian A;van de Loosdrecht AA;Jädersten M;Tobiasson M;Kosmider O;Follo MY;Thol F;Pinheiro RF;Santini V;Kotsianidis I;Boultwood J;Santos FPS;Schanz J;Kasahara S;Ishikawa T;Tsurumi H;Takaori-Kondo A;Kiguchi T;Polprasert C;Bennett JM;Klimek VM;Savona MR;Belickova M;Ganster C;Palomo L;Sanz G;Ades L;Della Porta MG;Elias HK;Smith AG;Werner Y;Patel M;Viale A;Vanness K;Neuberg DS;Stevenson KE;Menghrajani K;Bolton KL;Fenaux P;Pellagatti A;Platzbecker U;Heuser M;Valent P;Chiba S;Miyazaki Y;Finelli C;Voso MT;Shih LY;Fontenay M;Jansen JH;Cervera J;Atsuta Y;Gattermann N;Ebert BL;Bejar R;Greenberg PL;Cazzola M;Hellström-Lindberg E;Ogawa S;Papaemmanuil E
通讯作者：
Papaemmanuil E
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
1.7
作者：
Abu-Asab, M. S.;Abu-Asab, N.;Amri, H.
通讯作者：
Amri, H.
影响因子：
16.6
作者：
Cmero, Marek;Yuan, Ke;Macintyre, Geoff
通讯作者：
Macintyre, Geoff
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y